Separation of collagen‐bound and porous bone water transverse relaxation in mice: proposal of a multi‐step approach

The separation and quantification of collagen‐bound water (CBW) and pore water (PW) components of the cortical bone signal are important because of their different contribution to bone mechanical properties. Ultrashort TE (UTE) imaging can be used to exploit the transverse relaxation from CBW and PW, allowing their quantification. We tested, for the first time, the feasibility of UTE measurements in mice for the separation and quantification of the transverse relaxation of CBW and PW in vivo using three different approaches for T₂* determination. UTE sequences were acquired at 4.7 T in six mice with 10 different TEs (50–5000 μs). The transverse relaxation time T₂* of CBW (T₂*_cbw) and PW (T₂*_pw) and the CBW fraction (bwf) were computed using a mono‐exponential (i), a standard bi‐exponential (ii) and a new multi‐step bi‐exponential (iii) approach. Regions of interest were drawn at multiple levels of the femur and vertebral body cortical bone for each mouse. The sum of the normalized squared residuals (Res) and the homogeneity of variance were tested to compare the different methods. In the femur, approach (i) yielded mean T₂* ± standard deviation (SD) of 657 ± 234 μs. With approach (ii), T₂*_cbw, T₂*_pw and bwf were 464 ± 153 μs, 15 777 ± 10 864 μs and 57.6 ± 9.9%, respectively. For approach (iii), T₂*_cbw, T₂*_pw and bwf were 387 ± 108 μs, 7534 ± 2765 μs and 42.5 ± 6.2%, respectively. Similar values were obtained from vertebral bodies. Res with approach (ii) was lower than with the two other approaches (p < 0.007), but T₂*_pw and bwf variance was lower with approach (iii) than with approach (ii) (p < 0.048). We demonstrated that the separation and quantification of cortical bone water components with UTE sequences is feasible in vivo in mouse models. The direct bi‐exponential approach exhibited the best approximation to the measured signal curve with the lowest residuals; however, the newly proposed multi‐step algorithm resulted in substantially lower variability of the computed parameters. Copyright © 2016 John Wiley & Sons, Ltd.     

Characterization of trabecular bone density with ultra‐short echo‐time MRI at 1.5, 3.0 and 7.0 T – comparison with micro‐computed tomography

The goal of this study was to test the potential of ultra‐short echo‐time (UTE) MRI at 1.5, 3.0 and 7.0 T for depiction of trabecular bone structure (of the wrist bones), to evaluate whether T₂* relaxation times of bone water and parametric maps of T₂* of trabecular bone could be obtained at all three field strengths, and to compare the T₂* relaxation times with structural parameters obtained from micro‐computed tomography (micro‐CT) as a reference standard. Ex vivo carpal bones of six wrists were excised en bloc and underwent MRI at 1.5, 3.0 and 7.0 T in a whole‐body MR imager using the head coil. A three‐dimensional radial fat‐suppressed UTE sequence was applied with subsequent acquisitions, with six different echo times T_E of 150, 300, 600, 1200, 3500 and 7000 µs. The T₂* relaxation time and pixel‐wise computed T₂* parametric maps were compared with a micro‐computed‐tomography reference standard providing trabecular bone structural parameters including porosity (defined as the bone‐free fraction within a region of interest), trabecular thickness, trabecular separation, trabecular number and fractal dimension (D_k). T₂* relaxation curves and parametric maps could be computed from datasets acquired at all field strengths. Mean T₂* relaxation times of trabecular bone were 4580 ± 1040 µs at 1.5 T, 2420 ± 560 µs at 3.0 T and 1220 ± 300 µs at 7.0 T, when averaged over all carpal bones. A positive correlation of T₂* with trabecular bone porosity and trabecular separation, and a negative correlation of T₂* relaxation time with trabecular thickness, trabecular number and fractal dimension, was detected (p < 0.01 for all field strengths and micro‐CT parameters). We conclude that UTE MRI may be useful to characterize the structure of trabecular bone, comparable to micro‐CT. Copyright © 2014 John Wiley & Sons, Ltd.     

Correlations of cortical bone microstructural and mechanical properties with water proton fractions obtained from ultrashort echo time (UTE) MRI tricomponent T2* model

Mechanical and microstructural evaluations of cortical bone using ultrashort echo time magnetic resonance imaging (UTE‐MRI) have been performed increasingly in recent years. UTE‐MRI acquires considerable signal from cortical bone and enables quantitative bone evaluations. Fitting bone apparent transverse magnetization (T2*) decay using a bicomponent model has been regularly performed to estimate bound water (BW) and pore water (PW) in the quantification of bone matrix and porosity, respectively. Human cortical bone possesses a considerable amount of fat, which appears as MRI T2* signal oscillation and can subsequently lead to BW overestimation when using a bicomponent model. Tricomponent T2* fitting model has been developed to improve BW and PW estimations by accounting for fat contribution in the MRI signal. This study aimed to investigate the correlations of microstructural and mechanical properties of human cortical bone with water pool fractions obtained from a tricomponent T2* model. 135 cortical bone strips (~4 × 2 × 40 mm³) from tibial and femoral midshafts of 37 donors (61 ± 24 years old) were scanned using ten sets of dual‐echo 3D‐UTE‐Cones sequences (TE = 0.032–24.0 ms) on a 3 T MRI scanner for T2* fitting analyses. Average bone porosity and pore size were measured using microcomputed tomography (μCT) at 9 μm voxel size. Bone mechanical properties were measured using 4‐point bending tests. Using a tricomponent model, bound water fraction (Frac_BW) showed significant strong (R = 0.70, P < 0.01) and moderate (R = 0.58–0.62, P < 0.01) correlations with porosity and mechanical properties, respectively. Correlations of bone microstructural and mechanical properties with water pool fractions were higher for tricomponent model results compared with the bicomponent model. The tricomponent T2* fitting model is suggested as a useful technique for cortical bone evaluation where the MRI contribution of bone fat is accounted for.     

Evaluation of bound and pore water in cortical bone using ultrashort‐TE MRI

Bone water exists in different states with the majority bound to the organic matrix and to mineral, and a smaller fraction in ‘free’ form in the pores of cortical bone. In this study, we aimed to develop and evaluate ultrashort‐TE (UTE) MRI techniques for the assessment of T₂*, T₁ and concentration of collagen‐bound and pore water in cortical bone using a 3‐T clinical whole‐body scanner. UTE MRI, together with an isotope study using tritiated and distilled water (THO–H₂O) exchange, as well as gravimetric analysis, were performed on ten sectioned bovine bone samples. In addition, 32 human cortical bone samples were prepared for comparison between the pore water concentration measured with UTE MRI and the cortical porosity derived from micro‐computed tomography (μCT). A short T₂* of 0.27 ± 0.03 ms and T₁ of 116 ± 6 ms were observed for collagen‐bound water in bovine bone. A longer T₂* of 1.84 ± 0.52 ms and T₁ of 527 ± 28 ms were observed for pore water in bovine bone. UTE MRI measurements showed a pore water concentration of 4.7–5.3% by volume and collagen‐bound water concentration of 15.7–17.9% in bovine bone. THO–H₂O exchange studies showed a pore water concentration of 5.9 ± 0.6% and collagen‐bound water concentration of 18.1 ± 2.1% in bovine bone. Gravimetric analysis showed a pore water concentration of 6.3 ± 0.8% and collagen‐bound water concentration of 19.2 ± 3.6% in bovine bone. A mineral water concentration of 9.5 ± 0.6% was derived in bovine bone with the THO–H₂O exchange study. UTE‐measured pore water concentration is highly correlated (R² = 0.72, p < 0.0001) with μCT porosity in the human cortical bone study. Both bovine and human bone studies suggest that UTE sequences could reliably measure collagen‐bound and pore water concentration in cortical bone using a clinical scanner. Copyright © 2015 John Wiley & Sons, Ltd.     

Visualization of calcium phosphate cement in teeth by zero echo time 1H MRI at high field

¹H magnetic resonance imaging (MRI) by a zero echo time (ZTE) sequence is an excellent method to image teeth. Calcium phosphate cement (CPC) materials are applied in the restoration of tooth lesions, but it has not yet been investigated whether they can be detected by computed tomography (CT) or MRI. The aim of this study was to optimize high‐field ZTE imaging to enable the visualization of a new CPC formulation implanted in teeth and to apply this in the assessment of its decomposition in vivo. CPC was implanted in three human and three goat teeth ex vivo and in three goat teeth in vivo. An ultrashort echo time (UTE) sequence with multiple flip angles and echo times was applied at 11.7 T to measure T₁ and T₂* values of CPC, enamel and dentin. Teeth with CPC were imaged with an optimized ZTE sequence. Goat teeth implanted with CPC in vivo were imaged after 7 weeks ex vivo. T₂* relaxation of implanted CPC, dentin and enamel was better fitted by a model assuming a Gaussian rather than a Lorentzian distribution. For CPC and human enamel and dentin, the average T₂* values were 273 ± 19, 562 ± 221 and 476 ± 147 μs, respectively, the average T₂ values were 1234 ± 27, 963 ± 151 and 577 ± 41 μs, respectively, and the average T₁ values were 1065 ± 45, 972 ± 40 and 903 ± 7 ms, respectively. In ZTE images, CPC had a higher signal‐to‐noise‐ratio than dentin and enamel because of the higher water content. Seven weeks after in vivo implantation, the CPC‐filled lesions showed less homogeneous structures, a lower T₁ value and T₂* separated into two components. MRI by ZTE provides excellent contrast for CPC in teeth and allows its decomposition to be followed.     

Fast volumetric imaging of bound and pore water in cortical bone using three‐dimensional ultrashort‐TE (UTE) and inversion recovery UTE sequences

We report the three‐dimensional ultrashort‐TE (3D UTE) and adiabatic inversion recovery UTE (IR‐UTE) sequences employing a radial trajectory with conical view ordering for bi‐component T₂* analysis of bound water (T₂*^BW) and pore water (T₂*^PW) in cortical bone. An interleaved dual‐echo 3D UTE acquisition scheme was developed for fast bi‐component analysis of bound and pore water in cortical bone. A 3D IR‐UTE acquisition scheme employing multiple spokes per IR was developed for bound water imaging. Two‐dimensional UTE (2D UTE) and IR‐UTE sequences were employed for comparison. The sequences were applied to bovine bone samples (n = 6) and volunteers (n = 6) using a 3‐T scanner. Bi‐component fitting of 3D UTE images of bovine samples showed a mean T₂*^BW of 0.26 ± 0.04 ms and T₂*^PW of 4.16 ± 0.35 ms, with fractions of 21.5 ± 3.6% and 78.5 ± 3.6%, respectively. The 3D IR‐UTE signal showed a single‐component decay with a mean T₂*^BW of 0.29 ± 0.05 ms, suggesting selective imaging of bound water. Similar results were achieved with the 2D UTE and IR‐UTE sequences. Bi‐component fitting of 3D UTE images of the tibial midshafts of healthy volunteers showed a mean T₂*^BW of 0.32 ± 0.08 ms and T₂*^PW of 5.78 ± 1.24 ms, with fractions of 34.2 ± 7.4% and 65.8 ± 7.4%, respectively. Single‐component fitting of 3D IR‐UTE images showed a mean T₂*^BW of 0.35 ± 0.09 ms. The 3D UTE and 3D IR‐UTE techniques allow fast volumetric mapping of bound and pore water in cortical bone. Copyright © 2016 John Wiley & Sons, Ltd.     

UTE–ΔR2–ΔR2* combined MR whole‐brain angiogram using dual‐contrast superparamagnetic iron oxide nanoparticles

The ability to visualize whole‐brain vasculature is important for quantitative in vivo investigation of vascular malfunctions in cerebral small vessel diseases, including cancer, stroke and neurodegeneration. Transverse relaxation‐based ΔR₂ and ΔR₂* MR angiography (MRA) provides improved vessel–tissue contrast in animal deep brain with the aid of intravascular contrast agents; however, it is susceptible to orientation dependence, air–tissue interface artifacts and vessel size overestimation. Dual‐mode MRA acquisition with superparamagnetic iron oxide nanoparticles (SPION) provides a unique opportunity to systematically compare and synergistically combine both longitudinal (R₁) and transverse (ΔR₂ and ΔR₂*) relaxation‐based MRA. Through Monte Carlo (MC) simulation and MRA experiments in normal and tumor‐bearing animals with intravascular SPION, we show that ultrashort TE (UTE) MRA acquires well‐defined vascularization on the brain surface, minimizing air–tissue artifacts, and combined ΔR₂ and ΔR₂* MRA simultaneously improves the sensitivity to intracortical penetrating vessels and reduces vessel size overestimation. Consequently, UTE–ΔR₂–ΔR₂* combined MRA complements the shortcomings of individual angiograms and provides a strategy to synergistically merge longitudinal and transverse relaxation effects to generate more robust in vivo whole‐brain micro‐MRA. Copyright © 2016 John Wiley & Sons, Ltd.     

Evaluation of normal cadaveric Achilles tendon and enthesis with ultrashort echo time (UTE) magnetic resonance imaging and indentation testing

Entheses are regions where tendons and ligaments attach to bone, and are the primary target in seronegative and other diseases of the musculoskeletal (MSK) system. MRI has been widely used for visualizing features of inflammatory and degenerative MSK disease; however, normal tendons and entheses have short transverse relaxation times (T₂), and show little or no signal with conventional clinical MRI pulse sequences, making it difficult to investigate their MR properties. In this study we examined the normal MR morphology of the cadaveric Achilles tendon and enthesis at 3 T using novel three‐dimensional ultrashort echo time (3D UTE) Cones sequences, and at 11.7 T using conventional MRI sequences. We also studied the MR properties of the Achilles tendon and enthesis including T₂*, T₁, and magnetization transfer ratio (MTR). In addition, MT modeling of macromolecular proton fractions was investigated using 3D UTE Cones sequences at 3 T. Indentation testing was performed to investigate the mechanical properties of the tendons and entheses, and this was followed by histological examination. In total five specimens (<50 years) were investigated. On average, tendons and entheses respectively had T₂* values of 0.93 ± 0.48 ms and 2.77 ± 0.79 ms, T₁ values of 644 ± 22 ms and 780 ± 55 ms, MTRs of 0.373 ± 0.03 and 0.244 ± 0.009 with an MT power of 1000° and frequency offset of 2 kHz, and macromolecular proton fractions of 18.0 ± 2.2% and 13.9 ± 1.9%. Compared with the tendon, the enthesis generally had a longer T₂*, a longer T₁, a lower MTR, and a lower macromolecular proton fraction as well as both a higher Young's modulus and stiffness. Results from this study are likely to provide a useful baseline for identifying deviations from the normal in seronegative arthritis and other disease of the entheses.     

Ultrashort echo time magnetization transfer (UTE‐MT) imaging of cortical bone

Magnetization transfer (MT) imaging is one way to indirectly assess pools of protons with fast transverse relaxation. However, conventional MT imaging sequences are not applicable to short T₂ tissues such as cortical bone. Ultrashort echo time (UTE) sequences with T_E values as low as 8 µs can detect signals from different water components in cortical bone. In this study we aim to evaluate two‐dimensional UTE‐MT imaging of cortical bone and its application in assessing cortical bone porosity as measured by micro‐computed tomography (μCT) and biomechanical properties. In total, 38 human cadaveric distal femur and proximal tibia bones were sectioned to produce 122 rectangular pieces of cortical bone for quantitative UTE‐MT MR imaging, μCT, and biomechanical testing. Off‐resonance saturation ratios (OSRs) with a series of MT pulse frequency offsets (Δf) were calculated and compared with porosity assessed with μCT, as well as elastic (modulus, yield stress, and strain) and failure (ultimate stress, failure strain, and energy) properties, using Pearson correlation and linear regression. A moderately strong negative correlation was observed between OSR and μCT porosity (R² = 0.46–0.51), while a moderate positive correlation was observed between OSR and yield stress (R² = 0.25–0.30) and failure stress (R² = 0.31–0.35), and a weak positive correlation (R² = 0.09–0.12) between OSR and Young's modulus at all off‐resonance saturation frequencies. OSR determined with the UTE‐MT sequence provides quantitative information on cortical bone and is sensitive to μCT porosity and biomechanical function. Copyright © 2015 John Wiley & Sons, Ltd.     

Ultrashort echo time magnetization transfer (UTE‐MT) imaging and modeling: magic angle independent biomarkers of tissue properties

MRI biomarkers such as T₂, T₂* and T_1rho have been widely used, but are confounded by the magic angle effect. The purpose of this study is to investigate the use of the two‐dimensional ultrashort echo time magnetization transfer (UTE‐MT) sequence for potential magic angle independent MR biomarkers. Magnetization transfer was investigated in cadaveric Achilles tendon samples using the UTE‐MT sequence at five MT powers and five frequency offsets ranging from 2 to 50 kHz. The protocol was applied at five sample orientations ranging from 0 to 90° relative to the B₀ field. The results were analyzed with a two‐pool quantitative MT model. Multiple T_E data were also acquired and mono‐exponential T₂* was calculated for each orientation. Macromolecular proton fractions and exchange rates derived from UTE‐MT modeling did not appreciably change between the various orientations, whereas the T₂* relaxation time demonstrated up to a sixfold increase from 0° to 55°. The UTE‐MT technique with two‐pool modeling shows promise as a clinically compatible technique that is resistant to the magic angle effect. This method provides information on the macromolecular proton pool that cannot be directly obtained by other methods, including regular UTE techniques.     

Can ultrashort‐TE (UTE) MRI sequences on a 3‐T clinical scanner detect signal directly from collagen protons: freeze–dry and D2O exchange studies of cortical bone and Achilles tendon specimens

Ultrashort‐TE (UTE) sequences can obtain signal directly from short‐T ₂ , collagen‐rich tissues. It is generally accepted that bound and free water can be detected with UTE techniques, but the ability to detect protons directly on the collagen molecule remains controversial. In this study, we investigated the potential of UTE sequences on a 3‐T clinical scanner to detect collagen protons via freeze–drying and D ₂ O–H ₂ O exchange studies. Experiments were performed on bovine cortical bone and human Achilles tendon specimens, which were either subject to freeze–drying for over 66 h or D ₂ O–H ₂ O exchange for 6 days. Specimens were imaged using two‐ and three‐dimensional UTE with Cones trajectory techniques with a minimum TE of 8 μs at 3 T. UTE images before treatment showed high signal from all specimens with bi‐component T ₂ * behavior. Bovine cortical bone showed a shorter T ₂ * component of 0.36 ms and a longer T ₂ * component of 2.30 ms with fractions of 78.2% and 21.8% by volume, respectively. Achilles tendon showed a shorter T ₂ * component of 1.22 ms and a longer T ₂ * component of 15.1 ms with fractions of 81.1% and 18.9% by volume, respectively. Imaging after freeze–drying or D ₂ O–H ₂ O exchange resulted in either the absence or near‐absence of signal. These results indicate that bound and free water are the sole sources of UTE signal in bovine cortical bone and human Achilles tendon samples on a clinical 3‐T scanner. Protons on the native collagen molecule are not directly visible when imaged using UTE sequences. Copyright © 2016 John Wiley & Sons, Ltd.     

Manganese‐enhanced MRI of rat brain based on slow cerebral delivery of manganese(II) with silica‐encapsulated MnxFe1–xO nanoparticles

In this work, we report a monodisperse bifunctional nanoparticle system, MIO@SiO₂‐RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. In vivo MRI of rats injected intravenously with MIO@SiO₂‐RITC nanoparticles exhibited enhancement of the T₁ contrast in brain tissue, in particular a time‐delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of MIO@SiO₂‐RITC nanoparticles in the liver, resulting in the slow release of manganese(II) [Mn(II)] into the blood pool and, subsequently, accumulation in the brain tissue. Thus, T₁‐weighted contrast enhancement was clearly detected in the anatomic structure of the brain as time progressed. In addition, T₂*‐weighted images of the liver showed a gradual darkening effect. Here, we demonstrate the concept of the slow release of Mn(II) for neuroimaging. This new nanoparticle‐based manganese contrast agent allows one simple intravenous injection (rather than multiple infusions) of Mn(II) precursor, and results in delineation of the detailed anatomic neuroarchitecture in MRI; hence, this provides the advantage of the long‐term study of neural function. Copyright © 2013 John Wiley & Sons, Ltd.     

CEST MRI of sepsis‐induced acute kidney injury

Sepsis‐induced acute kidney injury (SAKI) is a major complication of kidney disease associated with increased mortality and faster progression. Therefore, the development of imaging biomarkers to detect septic AKI is of great clinical interest. In this study, we aimed to characterize the endogenous chemical exchange saturation transfer (CEST) MRI contrast in the lipopolysaccharide (LPS)‐induced SAKI mouse model and to investigate the use of CEST MRI for detecting such injury. We used a SAKI mouse model that was generated by i.p. injection of 10 mg/kg LPS. The resulting kidney injury was confirmed by the elevation of serum creatinine and histology. MRI assessments were performed 24 h after LPS injection, including CEST MRI at different B₁ strengths (1, 1.8 and 3 μT), T₁ mapping, T₂ mapping and conventional magnetization transfer contrast (MTC) MRI. The CEST MRI results were analyzed using Z‐spectra, in which the normalized water signal saturation (S_sat/S₀) is measured as a function of saturation frequency. Substantial decreases in CEST contrast were observed at both 3.5 and ? 3.5 ppm frequency offset from water at all B₁ powers, with the most significant difference obtained at a B₁ of 1.8 μT. The average S_sat/S₀ differences between injured and normal kidneys were 0.07 (0.55 ± 0.04 versus 0.62 ± 0.04, P = 0.0028) and 0.07 (0.50 ± 0.04 versus 0.57 ± 0.03, P = 0.0008) for 3.5 and ? 3.5 ppm, respectively. In contrast, the T₁ and T₂ relaxation times and MTC contrast in the injured kidneys did not show a significant change compared with the normal control. Our results showed that CEST MRI is more sensitive to the pathological changes in injured kidneys than the changes in T₁, T₂ and MTC effect, indicating its potential clinical utility for molecular imaging of renal diseases.     

Ultrashort‐TE MRI longitudinal study and characterization of a chronic model of asthma in mice: inflammation and bronchial remodeling assessment

Asthma is a chronic disease characterized by bronchial hyperresponsiveness (BHR), bronchial inflammation and remodeling. The great improvements in ¹H MRI ultrashort‐TE (UTE) sequences in the last decade have allowed lung images with high‐resolution and good signal‐to‐noise ratio to be obtained in parenchymal tissues. In this article, we present a UTE ¹H MRI high‐resolution study of a chronic model of asthma in mice with the aim to longitudinally assess the main features of asthma using a fully noninvasive approach. Balb/c mice (n = 6) were sensitized with ovalbumin over a period of 75 days. The control group (n = 3) received normal saline on the same days. MRI acquisitions were performed on days 0, 38 and 78 to study the inflammatory volumes and bronchial remodeling (peribronchial signal intensity index, PBSI). Plethysmographic studies were performed on days 0, 39 and 79 to assess BHR to methacholine using the enhanced pause (Penh) ratio. The average inflammatory volume measured by MRI in the ovalbumin group (15.6 ± 2.4 μL) was increased significantly relative to control mice (–0.3 ± 0.7 μL) on day 38. The inflammatory volume was larger (34.2 ± 3.1 μL) on day 78 in the ovalbumin group. PBSI was significantly higher in the ovalbumin group on day 78 (1.53 ± 0.08) relative to the control group (1.16 ± 0.10), but not on day 38. After sensitization, asthmatic mice presented BHR to methacholine on days 39 and 79. Penh ratios correlated significantly with the inflammatory volume on day 39 and with the PBSI on day 79. This study shows, for the first time, that high‐resolution UTE ¹H MRI of the lungs may allow the noninvasive quantification of peribronchial eosinophilic inflammation with airways occlusion by mucus and of bronchial remodeling in a murine asthma model that correlates with functional parameters. Copyright © 2013 John Wiley & Sons, Ltd.     

Three‐dimensional accurate detection of lung emphysema in rats using ultra‐short and zero echo time MRI

Emphysema is a life‐threatening pathology that causes irreversible destruction of alveolar walls. In vivo imaging techniques play a fundamental role in the early non‐invasive pre‐clinical and clinical detection and longitudinal follow‐up of this pathology. In the present study, we aimed to evaluate the feasibility of using high resolution radial three‐dimensional (3D) zero echo time (ZTE) and 3D ultra‐short echo time (UTE) MRI to accurately detect lung pathomorphological changes in a rodent model of emphysema.Porcine pancreas elastase (PPE) was intratracheally administered to the rats to produce the emphysematous changes. 3D ZTE MRI, low and high definition 3D UTE MRI and micro‐computed tomography images were acquired 4 weeks after the PPE challenge. Signal‐to‐noise ratios (SNRs) were measured in PPE‐treated and control rats. T₂* values were computed from low definition 3D UTE MRI. Histomorphometric measurements were made after euthanizing the animals. Both ZTE and UTE MR images showed a significant decrease in the SNR measured in PPE‐treated lungs compared with controls, due to the pathomorphological changes taking place in the challenged lungs. A significant decrease in T₂* values in PPE‐challenged animals compared with controls was measured using UTE MRI. Histomorphometric measurements showed a significant increase in the mean linear intercept in PPE‐treated lungs. UTE yielded significantly higher SNR compared with ZTE (14% and 30% higher in PPE‐treated and non‐PPE‐treated lungs, respectively).This study showed that optimized 3D radial UTE and ZTE MRI can provide lung images of excellent quality, with high isotropic spatial resolution (400 µm) and SNR in parenchymal tissue (>25) and negligible motion artifacts in freely breathing animals. These techniques were shown to be useful non‐invasive instruments to accurately and reliably detect the pathomorphological alterations taking place in emphysematous lungs, without incurring the risks of cumulative radiation exposure typical of micro‐computed tomography. Copyright © 2015 John Wiley & Sons, Ltd.     

Quantitative BOLD response of the renal medulla to hyperoxic challenge at 1.5 T and 3.0 T

The aim of this study was to gage the magnitude of changes of the apparent renal medullary transverse relaxation time (ΔT₂*) induced by inhalation of pure oxygen (O₂) or carbogen (95% O₂, 5% CO₂) versus baseline breathing of room air. Eight healthy volunteers underwent 2D multi‐gradient echo MR imaging at 1.5 T and 3.0 T. Parametrical T₂* relaxation time maps were computed and average T₂* was measured in regions of interest placed in the renal medulla and cortex. The largest T₂* changes were measured in the renal medulla, with a relative ?T₂* of 33.8 ± 22.0% (right medulla) and 34.7 ± 17.6% (left medulla) as compared to room air for oxygen breathing (p > 0.01), and 53.8 ± 23.9% and 53.5 ± 33.9% (p < 0.01) for carbogen breathing, respectively at 3 T. At 1.5 T, the corresponding values were 13.7 ± 18.5% and 24.1 ± 17.1% (p < 0.01) for oxygen breathing and 23.9 ± 17.2% and 38.9 ± 37.6% (p < 0.01) for carbogen breathing. As a result, we showed that renal medullary T₂* times responded strongly to inhalation of hyperoxic gases, which may be attributed to the hypoxic condition of the medulla and subsequent reduction in deoxyhemoglobin. Copyright © 2012 John Wiley & Sons, Ltd.     

39K and 23Na relaxation times and MRI of rat head at 21.1 T

At ultrahigh magnetic field strengths (B₀ ≥ 7.0 T), potassium (³⁹K) MRI might evolve into an interesting tool for biomedical research. However, ³⁹K MRI is still challenging because of the low NMR sensitivity and short relaxation times. In this work, we demonstrated the feasibility of ³⁹K MRI at 21.1 T, determined in vivo relaxation times of the rat head at 21.1 T, and compared ³⁹K and sodium (²³Na) relaxation times of model solutions containing different agarose gel concentrations at 7.0 and 21.1 T. ³⁹K relaxation times were markedly shorter than those of ²³Na. Compared with the lower field strength, ³⁹K relaxation times were up to 1.9‐ (T₁), 1.4‐ (T_2S) and 1.9‐fold (T_2L) longer at 21.1 T. The increase in the ²³Na relaxation times was less pronounced (up to 1.2‐fold). Mono‐exponential fits of the ³⁹K longitudinal relaxation time at 21.1 T revealed T₁ = 14.2 ± 0.1 ms for the healthy rat head. The ³⁹K transverse relaxation times were 1.8 ± 0.2 ms and 14.3 ± 0.3 ms for the short (T_2S) and long (T_2L) components, respectively. ²³Na relaxation times were markedly longer (T₁ = 41.6 ± 0.4 ms; T_2S = 4.9 ± 0.2 ms; T_2L = 33.2 ± 0.2 ms). ³⁹K MRI of the healthy rat head could be performed with a nominal spatial resolution of 1 × 1 × 1 mm³ within an acquisition time of 75 min. The increase in the relaxation times with magnetic field strength is beneficial for ²³Na and ³⁹K MRI at ultrahigh magnetic field strength. Our results demonstrate that ³⁹K MRI at 21.1 T enables acceptable image quality for preclinical research. Copyright © 2016 John Wiley & Sons, Ltd.     

Effect of anesthesia on renal R2* measured by blood oxygen level‐dependent MRI

Blood oxygen level‐dependent (BOLD) MRI is increasingly being used to assess renal tissue oxygenation during disease based on the transverse relaxation rate (R₂*). In preclinical small animal models, the requisite use of anesthesia during imaging may lead to functional changes which influence R₂* and confound results. The purpose of this study was to evaluate the effects of four common anesthetic compounds on renal R₂* in healthy mice. Five female ICR mice were imaged with BOLD MRI approximately 25 min after induction with isoflurane (Iso; 1% or 1.5%, delivered in 100% O₂), ketamine/xylazine (KX), sodium pentobarbital (PB) or 2,2,2‐tribromoethanol (TBE). A significant effect of anesthetic agent on R₂* was observed in all tissue layers of the kidney, including the cortex, outer stripe of the outer medulla (OSOM), inner stripe of the outer medulla (ISOM) and inner medulla (IM). Pairwise significant differences in R₂* between specific agents were found in the cortex, OSOM and ISOM, with the largest difference observed in the ISOM between 1.5% Iso (26.6 ± 1.7 s^–1) and KX (66.0 ± 7.1 s^–1). The difference between 1% Iso and KX in the ISOM was not abolished when KX was administered with supplemental 100% O₂ or when 1% Iso was delivered in 21% O₂, indicating that the fraction of inspired oxygen did not account for the observed differences. Our results indicate that the choice of anesthesia has a large influence on the observed R₂* in mouse kidney, and anesthetic effects must be considered in the design and interpretation of renal BOLD MRI studies. Copyright © 2015 John Wiley & Sons, Ltd.     

31P NMR relaxation of cortical bone mineral at multiple magnetic field strengths and levels of demineralization

Recent work has shown that solid‐state ¹H and ³¹P MRI can provide detailed insight into bone matrix and mineral properties, thereby potentially enabling differentiation of osteoporosis from osteomalacia. However, ³¹P MRI of bone mineral is hampered by unfavorable relaxation properties. Hence, accurate knowledge of these properties is critical to optimizing MRI of bone phosphorus. In this work, ³¹P MRI signal‐to‐noise ratio (SNR) was predicted on the basis of T₁ and T₂* (effective transverse relaxation time) measured in lamb bone at six field strengths (1.5–11.7 T) and subsequently verified by 3D ultra‐short echo‐time and zero echo‐time imaging. Further, T₁ was measured in deuterium‐exchanged bone and partially demineralized bone. ³¹P T₂* was found to decrease from 220.3 ± 4.3 µs to 98.0 ± 1.4 µs from 1.5 to 11.7 T, and T₁ to increase from 12.8 ± 0.5 s to 97.3 ± 6.4 s. Deuteron substitution of exchangeable water showed that 76% of the ³¹P longitudinal relaxation rate is due to ¹H–³¹P dipolar interactions. Lastly, hypomineralization was found to decrease T₁, which may have implications for ³¹P MRI based mineralization density quantification. Despite the steep decrease in the T₂*/T₁ ratio, SNR should increase with field strength as B₀^0.4 for sample‐dominated noise and as B₀^1.1 for coil‐dominated noise. This was confirmed by imaging experiments. Copyright © 2013 John Wiley & Sons, Ltd.     

Simultaneous evaluation of vascular morphology,blood volume and transvascular permeability using SPION‐based,dual‐contrast MRI: imaging optimization and feasibility test

Exploiting ultrashort‐T_E (UTE) MRI, T₁‐weighted positive contrast can be obtained from superparamagnetic iron oxide nanoparticles (SPIONs), which are widely used as a robust T₂‐weighted, negative contrast agent on conventional MR images. Our study was designed (a) to optimize the dual‐contrast MRI method using SPIONs and (b) to validate the feasibility of simultaneously evaluating the vascular morphology, blood volume and transvascular permeability using the dual‐contrast effect of SPIONs. All studies were conducted using 3 T MRI. According to numerical simulation, 0.15 mM was the optimal blood SPION concentration for visualizing the positive contrast effect using UTE MRI (T_E = 0.09 ms), and a flip angle of 40° could provide sufficient SPION‐induced enhancement and acceptable measurement noise for UTE MR angiography. A pharmacokinetic study showed that this concentration can be steadily maintained from 30 to 360 min after the injection of 29 mg/kg of SPIONs. An in vivo study using these settings displayed image quality and CNR of SPION‐enhanced UTE MR angiography (image quality score 3.5; CNR 146) comparable to those of the conventional, Gd‐enhanced method (image quality score 3.8; CNR 148) (p > 0.05). Using dual‐contrast MR images obtained from SPION‐enhanced UTE and conventional spin‐ and gradient‐echo methods, the transvascular permeability (water exchange index 1.76–1.77), cerebral blood volume (2.58–2.60%) and vessel caliber index (3.06–3.10) could be consistently quantified (coefficient of variation less than 9.6%; Bland–Altman 95% limits of agreement 0.886–1.111) and were similar to the literature values. Therefore, using the optimized setting of combined SPION‐based MRI techniques, the vascular morphology, blood volume and transvascular permeability can be comprehensively evaluated during a single session of MR examination. Copyright © 2015 John Wiley & Sons, Ltd.